Jon Chung, PhD

Senior Clinical Development Manager at Foundation Medicine

October 4, 2017

Breast cancer is an important example of how a better understanding of cancer biology can lead to more personalized and precise treatments that improve patient care and prognosis. Surgery, hormone therapy, and chemotherapy were the standard of care for decades, but research into the HER2 gene as a potential biomarker for certain types of breast cancer ultimately led to the first FDA-approved molecularly targeted therapy for breast cancer. Since then, we have continued to learn more about the various molecular subtypes of this disease. Finding new biomarkers for breast cancer could aid in the development of more therapies precisely targeted to those genomic alterations. The ultimate goal for all of us in oncology is to have personalized treatment options available for every person diagnosed with breast cancer.

The evolution of each breast cancer

Comprehensive genomic profiling (CGP) is one path toward achieving this vision of more personalized treatments. CGP has not only provided a better understanding of the genomic markers of breast cancer, but is helping to drive new research directions and new types of treatments.

This enhanced look into a tumor’s molecular underpinning has shown us that breast cancer – like other cancers – can be highly dynamic and evolve over time in response to therapy in each individual. Unfortunately, for some patients with advanced or refractory disease, obtaining a new sample may not be medically feasible.

Liquid biopsy has emerged as a non-invasive genomic profiling option that assesses circulating tumor DNA (ctDNA). FoundationACT®, our ctDNA assay, requires only a blood sample to probe for genomic markers that could help guide treatment. Importantly, this assay allows us to measure these markers both when a metastatic cancer arises and at different stages of its evolution.

Informing breast cancer treatment with liquid biopsy

We recently published new findings that support the value of this technique. In the study, Foundation Medicine and our collaborators across the country showed that FoundationACT was able to identify genomic alterations in the majority of a group of patients with estrogen receptor-positive (ER+) metastatic breast cancer. These potentially actionable alterations could inform treatment decisions as well as complement tissue-based testing.

Study results showed that 84% of ER+ breast cancer patients had evidence of ctDNA in the blood, and at least one genomic alteration was found in 78% of cases. In addition to ESR1 mutations, which are associated with resistance to aromatase inhibitor therapy, we identified genomic alterations that have been associated with response to a targeted therapy in metastatic breast cancer and may represent a new direction of treatment for patients refractory to standard therapies.

Furthermore, a subset of patients had matched tissue and ctDNA samples from approximately the same time period, which allowed for concordance analyses. This comparison showed that 89% of mutations detected in tissue were also detected in ctDNA, demonstrating that FoundationACT liquid biopsy could provide a complementary approach to tissue-based genomic testing.

More options for more patients

FoundationACT has already been shown to identify potentially actionable alterations in other types of cancer, including lung, gastrointestinal and prostate cancer. These new findings support the ability of FoundationACT to capture genomic alterations that may drive recurrence of disease or treatment resistance in ER+ breast cancer, helping to inform next steps for treatment, even for patients who may not be able to undergo a tissue biopsy. For patients who need a non-invasive genomic profiling option, FoundationACT could provide important information to navigate the complex dynamics of cancer.